Hantavirus hemorrhagic fever with renal syndrome (HFRS) is a hemorrhagic fever caused by hantavirus infection. Symptoms usually occur 2 weeks after exposure to the hantavirus and come in five distinct clinical stages: febrile (toxic), hypotensive, low urine production (oliguric), high urine production (diuretic), and recovery. Early symptoms include headache, lower back pain, nausea, vomiting, diarrhea, bloody stool, the appearance of spots on the skin, bleeding in the respiratory tract, and renal symptoms such as kidney swelling, proteinuria, and hematuria. During the hypotensive phase, blood pressure lowers due to microvascular leakage. Renal failure then causes the oliguric phase, before recovering and increasing urine production as disease progression improves. The severity of symptoms varies depending on which virus causes HFRS and ranges from mild illness to severe. The case fatality rate likewise varies by virus, from less than 1% up to 15%. HFRS is caused mainly by four viruses in Asia and Europe: Hantaan virus, Seoul virus, Puumala virus, and Dobrava-Belgrade virus. In East Asia, Hantaan virus is the most common cause of HFRS, causes a severe form of HFRS, and is spread by striped field mice. Seoul virus accounts for about a quarter of HFRS cases, causes a moderate form of the disease, and is found worldwide due to the global distribution of its natural reservoir, the brown rat. Puumala virus is the most common cause of HFRS in Russia and northern and central Europe, usually causes a mild form of HFRS, and is transmitted by the bank vole. Dobrava-Belgrade virus is the most common cause of HFRS in southern Europe, and varies in disease severity and natural reservoir depending on its genotype. A mild form of HFRS often called nephropathia epidemica (NE) is caused by Puumala virus and Dobrava-Belgrade virus. Transmission occurs mainly through inhalation of aerosols that contain rodent saliva, urine, or feces, but can also occur through contaminated food, bites, and scratches. Vascular endothelial cells and macrophages are the primary cells infected by hantaviruses, and infection causes abnormalities with blood clotting, all of which result in fluid leakage responsible for the more severe symptoms. Recovery from infection likely confers lifelong protection. The main way to prevent HFRS is to avoid or minimize contact with rodents that carry hantaviruses. Removing sources of food for rodents, safely cleaning up after them, and preventing them from entering one's house are all important means of protection. People who are at risk of interacting with infected rodents can wear masks to protect themselves. Bivalent vaccines that protect against Hantaan virus and Seoul virus are in use in China and South Korea. Initial diagnosis of infection can be made based on epidemiological information and symptoms. Confirmation of infection can be done by testing for hantavirus nucleic acid, proteins, or hantavirus-specific antibodies. Treatment of HFRS is supportive and depends on the phase of the disease and clinical presentation. Intravenous hydration, electrolyte therapy, and platelet transfusions may be performed, as well as intermittent hemodialysis for renal failure and continuous renal replacement therapy in critical cases. No specific antiviral drugs exist for hantavirus infection. More than 100,000 cases of HFRS occur each year. China is the most affected country in Asia, while Finland is the most affected country in Europe. More than 10,000 cases of NE are diagnosed annually. The distribution of viruses that cause HFRS is directly tied to the distribution of their natural reservoirs. Transmission is also greatly influenced by environmental factors such as rainfall, temperature, and humidity, which affect the rodent population and virus transmissibility. Outbreaks of HFRS have occurred throughout history, especially among soldiers during wartime who live in poor conditions. During the Korean War in the 1950s, an epidemic of HFRS occurred among United Nations soldiers stationed near the Hantan river. The outbreak was determined in the 1970s and 1980s to be caused by Hantaan virus, which was named after the river and which was the first hantavirus discovered. Other HFRS epidemics include an outbreak in Finland in World War Two among German and Finnish soldiers, caused by Puumala virus, and an outbreak in Croatia during the Balkan Wars, caused by Puumala virus and Dobrava-Belgrade virus.
Signs and symptoms
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